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MICR2222 - Medical Virology > L1/2 - Influenza > Flashcards

L1/2 - Influenza Flashcards

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USMLE® Step 1 flashcards
1
Q

Which influenza viruses have 8 segments?

A

A

B

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2
Q

Which influenza viruses have 7 segments

A

C

D

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3
Q

What are the 3 membrane proteins of influenza?

A

NA
HA
M2

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4
Q

Why do the segments not look like linear strands of DNA?

A

segments are wrapped up in RNA interactions and RNA-protein interactions

RNA-PROTEIN COMPLEXES

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5
Q

What are the two interactions that hold the RNA segment ends together

A

Watson-Crick interactions

PAN HANDLE STRUCTURE

5’ and 3’ ends interacts with RdRp

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6
Q

What protein does the RNA molecule interacts with?

A

NP - entirely covers

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7
Q

What 2 properties of NP

A

RNA binding via pos-charged residues in groove

NP-NP interaction via tail loop

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8
Q

What kind of conformation do influenza RNPs adopt?

A

hairpin

double helical conformation

antiparallel

held by NP-NP interactions

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9
Q

What 3 segments make the RdRp

A

PB1
PB2
PA

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10
Q

How can the 8 segments of influenza achieve more coding potential?

A

splicing

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11
Q

What is the 1st stage of the influenza virus life cycle?

A

virus attachment

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12
Q

How does virus attachment take place in influenza

A

mediated by HA

sialic acid recognised

target epithelial cells

virus internalised within endosome

different types of sialic acid linkage

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13
Q

Why does the Human and avian flu have different sialic acid linkages?

A

HA proteins show specificity to just one SA type

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14
Q

What sialic acid linkages does human influenza infect?

A

a2-6

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15
Q

What sialic acid linkages does avian influenza infect?

A

a2-3

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16
Q

How can specificity of sialic acid binding be switched?

A

single residue changes

e.g. Glu90

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17
Q

How does flu fuse with endosomes

A

pH 5 - mediates conformational shift in the HA protein

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18
Q

What is stage 2 of the influenza life cycle?

A

virus entry

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19
Q

How does the influenza virus escape the endosome?

A

fusion of viral & endosomal membranes

RNP segments released

mediated by HA protein and fusion peptide

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20
Q

How does the fusion peptide allow fusion to occur?

A

fusion peptide buried in HA0

HA1/HA2 cleavage = repositioning at amino-terminus

sticks into endosomal membrane

21
Q

What is the conformation change that happens to the fusion peptide?

A

2 helices in HA2 align

flips fusion peptide upwards

insertion

22
Q

what are the 2 CRITICAL FUNCTIONS of the HA protein?

A

1) virus attachment via sialic acid

2) virus entry by fusion of viral & endosomal membranes

23
Q

What is the 3rd stage of the influenza life cycle?

A

RNP release

24
Q

What happens during RNP release from matrix proteins?

A

mediated by M2

M2 x 4 = tetramer

M2 - influx of H+ ions into virion

25
Q

What is the 4th stage of the influenza life cycle?

A

RNP import

26
Q

What happens during RNP import

A

move from cytoplasm to nucleus

individual NP monomers - 2 import signals

27
Q

what is the ONLY NLS exposed on formed RNPs?

A

NLS1

recruits importin alpha

recruits importin b

RNP/importin complex binds pore and enters

28
Q

What is the 5th stage of the influenza life cycle?

A

RNA synthesis

29
Q

what are the 2 processes of RNA synthesis?

A

Transcription

Replication

30
Q

What is the polymerase structure for influenza?

A

3 subunits

4 holes lead to centre of the polymerase

31
Q

What happens during influenza transcription

A

results in 1 RNA transcript PER SEGMENT

resemble cellular mRNAs

32
Q

What are the 4 stage of influenza transcription?

A

RdRp PB2 binds cellular mRNA in nucleus - PA steals 5’ cap

RdRP + capped oligonucleotide bind to negative RNA genome

RdRP PB1 - use capped RNA, transcription

RdRp - move along templated, PB1 generates RNA transcript with polyA tail & 5’ cap

(NOT ENCAPSIDATED)

33
Q

What is the fate of influenza mRNA?

A

some stay in cytoplasm

some exported through nuclear pores - translated to viral proteins

34
Q

How are some influenza proteins imported back into the nucleus?

A

imported by NLS

35
Q

How can NS2 protein get back inside with nucleus without NLS?

A

it is an export signal - cannot have import

very small

36
Q

What are the 4 stages of influenza replication

A

RdRP binds 3’ end of RNA segment (no primer)

RdRp travels along segment - 3’ to 5’ direction - complimentary copy

NP wraps RNA = RNPs

cycles = amplification of genomes

37
Q

Why does transcription have to occur before replication in influenza?

A

requirement for NP

38
Q

What is the 6th stage of the influenza life cycle?

A

RNP export

39
Q

What is involved in RNP export (influenza)?

A

binding of M1 and NS2

  • RNPs associated with M1 in nucleus
  • NS2 binding M forming outer layer on RNP
  • NS2 has export signal, dominant over other signal - NS2 covers NLS
  • CRM1 binds to NS2 and helps export
40
Q

What protein, along with NS2, mediates RNP export in influenza?

A

CRM1
binds Ran-GTP
exits through NPC

41
Q

Where must RNPs reach?

A

the apical surface - with the 3 envelope proteins

42
Q

How do RNPs traffic by recycling endosomes?

A

interactions of RNPs with Rab11

M1 associates with cytoplasmic tails of the 3 envelope proteins

43
Q

What is another name for M1?

A

MASTER RECRUITER

44
Q

Why is viral release polarised towards apical surface and not the basolateral surface?

A

recycling endosomes only move to the apical surface

45
Q

What is the 7th stage of the influenza life cycle?

A

virus assembly

46
Q

What happens during virus assembly of influenza?

A

segments are selected

7+1 arrangement

47
Q

What is evidence for direct RNP interactions in virions between segments?

A

segments interact via RNA-RNA interactions

multiple interactions allow for sequence variations without impaired packaging

e.g. PB1-NP interaction

48
Q

What is the 8the stage of the influenza virus life cycle?

A

virus release

49
Q

What happens during influenza virus release?

A

NA solves the issue of binding on the sialic acid of the old cell

NA cleaves sialic acid from previously infected cell - only new ones infected

MICR2222 - Medical Virology (13 decks)

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